Inmaculada Alonso-Abreu

Colonoscopy versus Fecal Immunochemical Testing in Colorectal-Cancer Screening

BACKGROUND Colonoscopy and fecal immunochemical testing (FIT) are accepted strategies for colorectal-cancer screening in the average-risk population. METHODS In this randomized, controlled trial involving asymptomatic adults 50 to 69 years of age, we compared one-time colonoscopy in 26,703 subjects with FIT every 2 years in 26,599 subjects. The primary outcome was the rate of death from colorectal cancer at 10 years. This interim report describes rates of participation, diagnostic findings, and occurrence of major complications at completion of the baseline screening. Study outcomes were analyzed in both intention-to-screen and as-screened populations. RESULTS The rate of participation was higher in the FIT group than in the colonoscopy group (34.2% vs. 24.6%, P<0.001). Colorectal cancer was found in 30 subjects (0.1%) in the colonoscopy group and 33 subjects (0.1%) in the FIT group (odds ratio, 0.99; 95% confidence interval [CI], 0.61 to 1.64; P=0.99). Advanced adenomas were detected in 514 subjects (1.9%) in the colonoscopy group and 231 subjects (0.9%) in the FIT group (odds ratio, 2.30; 95% CI, 1.97 to 2.69; P<0.001), and nonadvanced adenomas were detected in 1109 subjects (4.2%) in the colonoscopy group and 119 subjects (0.4%) in the FIT group (odds ratio, 9.80; 95% CI, 8.10 to 11.85; P<0.001). CONCLUSIONS Subjects in the FIT group were more likely to participate in screening than were those in the colonoscopy group. On the baseline screening examination, the numbers of subjects in whom colorectal cancer was detected were similar in the two study groups, but more adenomas were identified in the colonoscopy group. (Funded by Instituto de Salud Carlos III and others; ClinicalTrials.gov number, NCT00906997.).

Time trends and impact of upper and lower gastrointestinal bleeding and perforation in clinical practice.

OBJECTIVES:Changing patterns in medical practice may contribute to temporal changes in the incidence of upper and lower gastrointestinal (GI) complications. There are limited data on the incidence of lower GI complications in clinical practice and most studies that have been done have serious methodological limitations to inferring the actual burden of this problem. The aims of this study were to analyze time trends of hospitalizations resulting from GI complications originating both from the upper and lower GI tract in the general population, and to determine the risk factors, severity, and clinical impact of these GI events.METHODS:This was a population-based study of patients hospitalized because of GI complications in 10 general hospitals between 1996 and 2005 in Spain. We report the age- and gender-specific rates, estimate the regression coefficients of the upper and lower GI event trends, and evaluate the severity and associated risk factors. GI hospitalization charts were validated by an independent review of large random samples of unspecific and specific codes distributed among all hospitals and study years.RESULTS:Upper GI complications fell from 87/100,000 persons in 1996 to 47/100,000 persons in 2005, whereas lower GI complications increased from 20/100,000 to 33/100,000. Overall, mortality rates decreased, but the case fatality remained constant over time. Lower GI events had a higher mortality rate (8.8 vs. 5.5%), a longer hospitalization (11.6±13.9 vs. 7.9±8.8 days), and higher resource utilization than did upper GI events. The use of nonsteroidal anti-inflammatory drugs (NSAIDs) without concomitant proton pump inhibitor was more frequently recorded among upper GI complications than among lower GI complications. When comparing upper GI events with lower GI events, we found that male gender (adjusted odds ratio (OR): 1.94; 95% confidence interval (CI): 1.70–2.21), and recorded NSAID use (OR: 1.92; 95% CI: 1.60–2.30) were associated to a greater extent with upper GI events, whereas older age (OR: 0.83; 95% CI: 0.77–0.89), number of comorbidities (OR: 0.91; 95% CI: 0.86–0.96), and having a diagnosis in recent years (OR: 0.92; 95% CI: 0.90–0.94) were all associated to a greater extent with lower GI events than with upper GI events after adjusting for age, sex, hospitalization, and discharge year.CONCLUSIONS:Over the past decade, there has been a progressive change in the overall picture of GI events leading to hospitalization, with a clear decreasing trend in upper GI events and a significant increase in lower GI events, causing the rates of these two GI complications to converge. Overall, mortality has also decreased, but the in-hospital case fatality of upper or lower GI complication events has remained constant. It will be a challenge to improve future care in this area unless we develop new strategies to reduce the number of events originating in the lower GI tract, as well as reducing their associated mortality.

Risk of Advanced Proximal Neoplasms According to Distal Colorectal Findings: Comparison of Sigmoidoscopy-Based Strategies

BACKGROUND Screening for colorectal cancer with sigmoidoscopy benefits from the fact that distal findings predict the risk of advanced proximal neoplasms (APNs). This study was aimed at comparing the existing strategies of postsigmoidoscopy referral to colonoscopy in terms of accuracy and resources needed. METHODS Asymptomatic individuals aged 50-69 years were eligible for a randomized controlled trial designed to compare colonoscopy and fecal immunochemical test. Sigmoidoscopy yield was estimated from results obtained in the colonoscopy arm according to three sets of criteria of colonoscopy referral (from those proposed in the UK Flexible Sigmoidoscopy, Screening for COlon REctum [SCORE], and Norwegian Colorectal Cancer Prevention [NORCCAP] trials). Advanced neoplasm detection rate, sensitivity, specificity, and number of individuals needed to refer for colonoscopy to detect one APN were calculated. Logistic regression analysis was performed to identify distal findings associated with APN. All statistical tests were two-sided. RESULTS APN was found in 255 of 5059 (5.0%) individuals. Fulfillment of UK (6.2%), SCORE (12.0%), and NORCCAP (17.9%) criteria varied statistically significantly (P < .001). The NORCCAP strategy obtained the highest sensitivity for APN detection (36.9%), and the UK approach reached the highest specificity (94.6%). The number of individuals needed to refer for colonoscopy to detect one APN was 6 (95% confidence interval [CI] = 4 to 7), 8 (95% CI = 6 to 9), and 10 (95% CI = 8 to 12) when the UK, SCORE, and NORCCAP criteria were used, respectively. The logistic regression analysis identified distal adenoma ≥10 mm (odds ratio = 3.77; 95% CI = 2.52 to 5.65) as the strongest independent predictor of APN. CONCLUSIONS Whereas the NORCCAP criteria achieved the highest sensitivity for APN detection, the UK recommendations benefited from the lowest number of individuals needed to refer for colonoscopy.

Uptake of Colon Capsule Endoscopy vs Colonoscopy for Screening Relatives of Patients With Colorectal Cancer

BACKGROUND & AIMS The efficacy of screening colonoscopy in first-degree relatives (FDRs) of patients with colorectal cancer (CRC) is limited by suboptimal uptake. We compared screening uptake of colon capsule endoscopy (CCE) vs colonoscopy in this population. METHODS We performed a prospective study of 329 asymptomatic FDRs of patients with CRC who were randomly assigned to groups examined by CCE (PillCam, second generation; n = 165) or colonoscopy (n = 164) at a tertiary hospital in Spain from July 2012 through December 2013. Crossover was permitted for patients who did not wish to undergo the assigned procedure. Subjects assigned to CCE who had a significant lesion (polyp ≥ 10 mm, >2 polyps of any size, or CRC) were invited to undergo colonoscopy. RESULTS One hundred twenty subjects in the CCE group and 113 in the colonoscopy group were eligible for inclusion. In the intention-to-screen analysis, uptake was similar between groups (55.8% CCE vs 52.2% colonoscopy; odds ratio [OR], 0.86; 95% confidence interval [CI], 0.51-1.44; P = .57); 57.4% of subjects crossed over from the CCE group, and 30.2% crossed over from the colonoscopy group (OR, 3.11; 95% CI, 1.51-6.41; P = .002). Unwillingness to repeat bowel preparation in the case of a positive result was the main reason that subjects assigned to the CCE group crossed over; fear of colonoscopy was the reason that most patients in this group crossed over. A significant lesion was detected in 14 subjects (11.7%) in the CCE group and 13 subjects (11.5%) in the colonoscopy group (OR, 1.02; 95% CI, 0.45-2.26; P = .96). CONCLUSIONS In a prospective study, similar numbers of FDRs of patients with CRC assigned to undergo CCE or colonoscopy agreed to participate, but most preferred to undergo colonoscopy. CCE was as effective as colonoscopy in detecting significant lesions; it could be a valid rescue strategy for subjects who reject screening colonoscopy. ClinicalTrials.gov number: NCT01557101.

Risk of Advanced Neoplasia in First-Degree Relatives with Colorectal Cancer: A Large Multicenter Cross-Sectional Study

Background First-degree relatives (FDR) of patients with colorectal cancer have a higher risk of developing colorectal cancer than the general population. For this reason, screening guidelines recommend colonoscopy every 5 or 10 y, starting at the age of 40, depending on whether colorectal cancer in the index-case is diagnosed at <60 or ≥60 y, respectively. However, studies on the risk of neoplastic lesions are inconclusive. The aim of this study was to determine the risk of advanced neoplasia (three or more non-advanced adenomas, advanced adenoma, or invasive cancer) in FDR of patients with colorectal cancer compared to average-risk individuals (i.e., asymptomatic adults 50 to 69 y of age with no family history of colorectal cancer). Methods and Findings This cross-sectional analysis includes data from 8,498 individuals undergoing their first lifetime screening colonoscopy between 2006 and 2012 at six Spanish tertiary hospitals. Of these individuals, 3,015 were defined as asymptomatic FDR of patients with colorectal cancer (“familial-risk group”) and 3,038 as asymptomatic with average-risk for colorectal cancer (“average-risk group”). The familial-risk group was stratified as one FDR, with one family member diagnosed with colorectal cancer at ≥60 y (n = 1,884) or at <60 y (n = 831), and as two FDR, with two family members diagnosed with colorectal cancer at any age (n = 300). Multiple logistic regression analysis was used for between-group comparisons after adjusting for potential confounders (age, gender, and center). Compared with the average-risk group, advanced neoplasia was significantly more prevalent in individuals having two FDR with colorectal cancer (odds ratio [OR] 1.90; 95% confidence interval [CI] 1.36–2.66, p < 0.001), but not in those having one FDR with colorectal cancer diagnosed at ≥60 y (OR 1.03; 95% CI 0.83–1.27, p = 0.77) and <60 y (OR 1.19; 95% CI 0.90–1.58, p = 0.20). After the age of 50 y, men developed advanced neoplasia over two times more frequently than women and advanced neoplasia appeared at least ten y earlier. Fewer colonoscopies by 2-fold were required to detect one advanced neoplasia in men than in women. Major limitations of this study were first that although average-risk individuals were consecutively included in a randomized control trial, this was not the case for all individuals in the familial-risk cohort; and second, the difference in age between the average-risk and familial-risk cohorts. Conclusions Individuals having two FDR with colorectal cancer showed an increased risk of advanced neoplasia compared to those with average-risk for colorectal cancer. Men had over 2-fold higher risk of advanced neoplasia than women, independent of family history. These data suggest that screening colonoscopy guidelines should be revised in the familial-risk population.

Early Colonoscopy Improves the Outcome of Patients With Symptomatic Colorectal Cancer

BACKGROUND: Long waiting times from early symptoms to diagnosis and treatment may influence the staging and prognosis of patients with colorectal cancer. We analyzed the effect of colonoscopy timing on the outcome of these patients. OBJECTIVE: This study aimed to compare the outcome (tumoral staging and long-term survival) of patients with suspected colorectal cancer according to diagnostic colonoscopy timing. DESIGN: This study is an analysis of a prospectively maintained database. SETTINGS: The study was conducted at the Open Access Endoscopy Service of the tertiary public healthcare center Hospital Universitario de Canarias, in the Spanish island of Tenerife. PATIENTS: Consecutive patients diagnosed of colorectal cancer between February 2008 and October 2010, fulfilling 1 or more National Institute for Health and Clinical Excellence criteria, were assigned to early colonoscopy (<30 days from referral) or to standard-schedule colonoscopy at the discretion of the referring physician. Tumor staging (TNM classification) at diagnosis and long-term survival after treatment were compared in both strategies. MAIN OUTCOME MEASURES: The primary outcomes measured were the stage at presentation and overall survival, as determined by prompt or standard referral. RESULTS: Overall, 257 patients with colorectal cancer were diagnosed (101 at early colonoscopy and 156 at standard-schedule colonoscopy). TNM stages I and II were found in 52 (54.2%) and 60 (41.7%) patients in the early colonoscopy group and standard-schedule colonoscopy group. Stage IV was confirmed in 13 patients (13.5%) diagnosed in the early colonoscopy group and in 40 (28%) detected in the standard-schedule colonoscopy group. Survival rates at 12 and 60 months after treatment were significantly higher in the early colonoscopy group compared with the standard-schedule colonoscopy group (p < 0.001). LIMITATIONS: Controlled randomization of early versus standard-referral colonoscopy, size and scope of analysis, the time interval from symptom onset to first physician assessment, and the different locations of colorectal cancer between groups were limitations of the study. CONCLUSIONS: Colonoscopy within 30 days from referral improves outcome in patients with symptomatic colorectal cancer. See Video Abstract at http://journals.lww.com/dcrjournal/Pages/videogallery.aspx.

Genetic susceptibility in the development of colorectal adenomas according to family history of colorectal cancer: Genetic susceptibility to colorectal adenomas

Our study aimed to evaluate the relevance of genetic susceptibility in the development of colorectal adenomas (CRA) and its relationship with the presence of family history of colorectal cancer (CRC). Genomic DNA from 750 cases (first degree relatives of patients with CRC) and 750 controls (subjects with no family history of CRC) was genotyped for 99 single nucleotide polymorphisms (SNPs) previously associated with CRC/CRA risk by GWAS and candidate gene studies by using the MassArray™ (Sequenom) platform. Cases and controls were matched by gender, age and histological lesion. Eight hundred and fifty‐eight patients showed no neoplastic lesions, whereas 288 patients showed low‐risk adenomas, and 354 patients presented high‐risk adenomas. Two SNPs (rs10505477, rs6983267) in the CASC8 gene were associated with a reduced risk of CRA in controls (log‐additive models, OR: 0.67, 95%CI:0.54–0.83, and OR:0.66, 95%CI:0.54–0.84, respectively). Stratified analysis by histological lesion revealed the association of rs10505477 and rs6983267 variants with reduced risk of low‐ and high‐risk adenomas in controls, being this effect stronger in low‐risk adenomas (log‐additive models, OR:0.63, 95%CI:0.47–0.84 and OR:0.64, 95%CI:0.47–0.86, respectively). Moreover, 2 SNPs (rs10795668, rs11255841) in the noncoding LINC00709 gene were significantly associated with a reduced risk of low‐risk adenomas in cases (recessive models, OR:0.22, 95%CI:0.06–0.72, and OR:0.08, 95%CI:0.03–0.61) and controls (dominant models, OR:0.50, 95%CI:0.34–0.75, and OR:0.52, 95%CI:0.35–0.78, respectively). In conclusion, some variants associated with CRC risk (rs10505477, rs6983267, rs10795668 and rs11255841) are also involved in the susceptibility to CRA and specific subtypes. These associations are influenced by the presence of family history of CRC.